The Identification of Critical m6A RNA Methylation Regulators as Malignant Prognosis Factors in Prostate Adenocarcinoma

RNA methylation accounts for over 60% of all RNA modifications, and N-6-methyladenosine (m(6)A) is the most common modification on mRNA and lncRNA of human beings. It has been found that m(6)A modification occurs in microRNA, circRNA, rRNA, and tRNA, etc. The m(6)A modification plays an important role in regulating gene expression, and the abnormality of its regulatory mechanism refers to many human diseases, including cancers. Pitifully, as it stands there is a serious lack of knowledge of the extent to which the expression and function of m(6)A RNA methylation can influence prostate cancer (PC). Herein, we systematically analyzed the expression levels of 35 m(6)A RNA methylation regulators mentioned in literatures among prostate adenocarcinoma patients in the Cancer Genome Atlas (TCGA), finding that most of them expressed differently between cancer tissues and normal tissues with the significance of p < 0.05. Utilizing consensus clustering, we divided PC patients into two subgroups based on the differentially expressed m(6)A RNA methylation regulators with significantly different clinical outcomes. To appraise the discrepancy in total transcriptome between subgroups, the functional enrichment analysis was conducted for differential signaling pathways and cellular processes. Next, we selected five critical genes by the criteria that the regulators had a significant impact on prognosis of PC patients from TCGA through the last absolute shrinkage and selection operator (LASSO) Cox regression and obtained a risk score by weighted summation for prognosis prediction. The survival analysis curve and receiver operating characteristic (ROC) curve showed that this signature could excellently predict the prognosis of PC patients. The univariate and multivariate Cox regression analyses proved the independent prognostic value of the signature. In summary, our effort revealed the significance of m(6)A RNA methylation regulators in prostate cancer and determined a m(6)A gene expression classifier that well predicted the prognosis of prostate cancer.